This program project grant in venereal diseases deals with four major areas of research: (1) Studies of gonococci-human leukocyte interactions suggest that virulent gonococci have antiphagocytic surface factors and attach to the surface membrane of phagocytic leukocytes. Optimal attachment is complement dependent and unrelated to the metabolic events of the leukocyte. (2) Conditions for exponential growth in liquid culture and easy monitoring of growth have been worked out for three gonococcal isolates, all colony Type 4. Growth conditions were found under which gonococci exhibit a "tolerant" response to penicillins, i.e., the bacteria are still inhibited in their growth at the normal minimum inhibitory concentration (M.I.C.) of penicillin, however, bacterial lysis no longer occurs. This phenomenon is reminiscent of the behavior of autolysin-defective pneumococci. Experiments are in progress to explore the nature of control of autolysin activity in gonococci. (3) An in vitro model has been developed to study spirochete-human monocyte interaction. Motile, virulent T. pallidum attach to the surface membrane whereas heated non-motile organisms remain free in the extracellular medium. Attachment is polar and neither serum nor complement-dependent. Sera from patients with primary and secondary syphilis and from rabbits convalescing from syphilitic orchitis does not promote ingestion. (4) In the study of the biology of Trichomonas vaginalis the biochemistry, pathogenicity and metronidazole sensitivity of freshly isolated strains and those cultivated in vitro are being compared. Preliminary observations suggest that carbohydrate enzymes are similar but that hydrolase and protease activity differs significantly.